ESTROGEN REPLACEMENT THERAPY DECREASES HYPERANDROGENICITY AND IMPROVES GLUCOSE-HOMEOSTASIS AND PLASMA-LIPIDS IN POSTMENOPAUSAL WOMEN WITH NONINSULIN-DEPENDENT DIABETES-MELLITUS

Hyperandrogenicity in women is closely associated with insulin resista nce and a risk factor for cardiovascular disease and noninsulin-depend ent diabetes mellitus (NIDDM). Therefore, 25 postmenopausal women with NIDDM and sex hormone-binding globulin values less than 60 nmol/L, as an indicator of a moderate hyperandrogenicity, were treated with 2 mg 17-beta-estradiol orally for 3 months in a double-blind, cross-over, placebo-controlled trial. During the last 16 days of active treatment, 1 mg norethisterone acetate was added for 10 days for endometrial pro tection. Blood glucose, glycosylated hemoglobin, insulin, c-peptide, l ipoprotein profile, sex steroid hormones, GK, and insulin-like growth factor I (IGF-I) were measured, and insulin sensitivity was determined by the euglycemic hyperinsulinemic clamp method. All metabolic measur ements were taken at baseline and after 68 days of active or placebo t reatment. Estradiol treatment, compared with the placebo period, was f ollowed by a marked increase of sex hormone-binding globulin and a dec rease of free testosterone. Blood glucose, glycosylated hemoglobin, c- peptide, total cholesterol, low-density lipoprotein cholesterol, and I GF-1 decreased significantly (P < 0.01-P < 0.001), whereas high densit y lipoprotein cholesterol rose (P < 0.001). In conclusion, estrogen re placement therapy in postmenopausal women with NIDDM ameliorated hyper androgenicity, and this was accompanied by marked improvements in gluc ose homeostasis and lipoprotein profile.